Case Report: Successful treatment of late-onset immune checkpoint inhibitor-associated membranous nephropathy in a patient with advanced renal cell carcinoma.

Background: Diagnosing immune checkpoint inhibitor (ICI)-associated nephritis can be challenging since it is a rare complication of therapy, associated with a spectrum of immune-mediated pathologies, and can present months after ICI therapy discontinuation (i.e., late-onset). ICIs are increasingly administered in combination with other cancer therapies with associated nephrotoxicity, further obfuscating the diagnosis of ICI-associated nephritis. In this report, we describe the first suspected case of late-onset ICI-associated membranous nephropathy (MN) in a patient with metastatic clear cell renal cell carcinoma (RCC) who had discontinued ICI therapy 6 months prior to presentation. Prompt recognition of the suspected late-onset immune-related adverse event (irAE) resulted in the successful treatment of MN and continuation of RCC therapy. Case presentation: A 57-year-old man with metastatic clear cell RCC was responsive to third-line RCC therapy with lenvatinib (oral TKI) and everolimus (oral mTOR inhibitor) when he presented with nephrotic range proteinuria and acute kidney injury (AKI). His kidney biopsy revealed probable secondary MN with subendothelial and mesangial immune complex deposits and negative staining for both phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A). While a diagnosis of paraneoplastic MN could not be excluded, the patient was responding to cancer therapy and had tumor regression. However, 6 months prior to presentation, the patient had received pembrolizumab, an ICI, with his first-line RCC treatment. Due to concern that the patient may be presenting with late-onset ICI-associated MN, he was effectively treated with rituximab, which allowed for his continued RCC therapy. Conclusion: This report highlights the first case of suspected late-onset ICI-associated MN and the increasing complexity of recognizing renal irAEs. With the growing indications for the use of ICIs in combination with other cancer therapies, recognizing the various presentations of ICI-immune nephritis can help guide patient management and treatment.

Preoperative blood pressure and risk of delayed graft function in deceased donor kidney transplantation.

BACKGROUND: In kidney transplantation, delayed graft function (DGF) is associated with increased morbidity and a higher risk of graft failure. Prior research suggests that chronic hypotension increases DGF risk, but the relationship of preoperative blood pressure to DGF is unclear. METHODS: In this single center study of adult deceased donor kidney transplant recipients transplanted between 2015 and 2019, we evaluated the question of whether preoperative mean arterial pressure (MAP) affected DGF risk. Additionally, we investigated whether the risk of DGF was moderated by certain donor and recipient characteristics. For recipient characteristics associated with increased DGF risk and preoperative MAP, we performed a mediation analysis to estimate the proportion of DGF risk mediated through preoperative MAP. RESULTS: Among 562 deceased donor kidney recipients, DGF risk decreased as preoperative MAP increased, with a 2% lower risk per 1 mm Hg increase in MAP. This increased risk was similar, with no statistically significant interaction effect between preoperative MAP and donor (donation after circulatory death) and recipient characteristics (diabetes, body mass index, and use of anti-hypertensive medications). Preoperative MAP was negativity correlated with recipient BMI and duration of pre transplant dialysis. On mediation analysis, MAP accounted for 12% and 16% of the DGF risk associated with recipient BMI and pre-transplant dialysis duration, respectively. CONCLUSION: In deceased donor kidney transplantation, each 1 mm Hg increase in preoperative MAP was associated with 2% lower DGF risk. Preoperative MAP was influenced by recipient BMI and dialysis duration, and likely contributes to some of the high DGF risk from obesity and long dialysis vintage.

Sodium and Potassium Dysregulation in the Patient With Cancer.

Sodium and potassium disorders are pervasive in patients with cancer. The causes of these abnormalities are wide-ranging, are often primary or second-order consequences of the underlying cancer, and have prognostic implications. The approach to hyponatremia should focus on cancer-related etiologies, such as syndrome of inappropriate antidiuretic hormone, to the exclusion of other causes. Hypernatremia in non-iatrogenic forms is generally due to water loss rather than excessive sodium intake. Debilitated or dependent patients with cancer are particularly vulnerable to hypernatremia. Hypokalemia can occur in patients with cancer due to gastrointestinal disturbances, resulting from decreased intake or increased losses. Renal losses can occur as a result of excessive mineralocorticoid secretion or therapy-related nephrotoxicity. The approach to hyperkalemia should be informed by historical and laboratory clues, and pseudohyperkalemia is particularly common in patients with hematological cancers. Hyperkalemia can be seen in primary or metastatic disease that interrupts the adrenal axis. It can also develop as a consequence of immunotherapy, which can cause adrenalitis or hypophysitis. Tumor lysis syndrome (TLS) is defined by the development of hyperkalemia and is a medical emergency. Awareness of the electrolyte abnormalities that can befall patients with cancer is vital for its prompt recognition and management.

Impact of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Renal Function in Chronic Kidney Disease Patients Undergoing Coronary Angiography.

BACKGROUND: Cardiac catheterizations and coronary angiography are minimally invasive methods for studying the heart and the coronary arteries, using iodinated radiocontrast agents which can cause acute kidney injury (AKI). Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) are widely used due to their well-established benefit in coronary artery disease and renal protection in diabetes mellitus. Renin-angiotensin-aldosterone system inhibitors can induce AKI in some patients. METHOD: This study analyzed the effect of radiocontrast media used for coronary angiography on renal function in patients with chronic kidney disease (CKD) stages 2-5 who also took ACE inhibitors/ARB medications. Information was collected from the electronic medical records of 116 cases to determine changes in serum creatinine following angiography.  Result: The average age of patients was 65.2 ± 12.3 years. There were 89 men (76.7%) and 27 women (23.3%). Six patients had documented ACE inhibitor discontinuation, and one patient had documented ARB discontinuation prior to their procedures. Based on the criteria of an increase in serum creatinine (SCr) by ≥0.3 mg/dl within 48 hours, 19 cases (16.4%) had AKI. Based on the criteria of increasing in SCr to ≥ 1.5 times baseline, AKI developed in 2 cases (1.7%) on day 1, 4 cases (3.5%) on day 2, and 7 cases (6.0%) on day 3 after coronary angiography. CONCLUSION: This study suggests that the continuation of ACE inhibitors/ARB does not appear to have any important effect or association with changes in renal function, within one-month post angiography in patients with CKD stages 2-5.

Risk of ischemic stroke in patients with polymyositis and dermatomyositis: a systematic review and meta-analysis.

Several chronic inflammatory disorders, such as rheumatoid arthritis and systemic lupus erythematosus, have been demonstrated to increase ischemic stroke risk, but the data on polymyositis (PM) and dermatomyositis (DM) remain unclear. We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio or standardized incidence ratio comparing ischemic risk in patients with PM/DM versus non-PM/DM participants. Pooled risk ratio and 95 % confidence intervals were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Three cohort studies were identified and included in our data analysis. The pooled risk ratio of ischemic stroke in patients with PM/DM was 1.61 (95 % CI 1.28-2.02). The statistical heterogeneity of this meta-analysis was insignificant with an I (2) of 0 %. Our study demonstrated a statistically significant increased ischemic stroke risk among patients with PM/DM.

Risk of coronary artery disease in patients with systemic sclerosis: a systematic review and meta-analysis.

Several chronic inflammatory disorders, such as rheumatoid arthritis and systemic lupus erythematosus, have been shown to increase coronary artery disease (CAD) risk but the data on systemic sclerosis (SSc) is unclear. We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing CAD risk in patients with SSc versus non-SSc participants. Pooled risk ratio and 95 % confidence intervals were calculated using a random effect, generic inverse variance method. Four studies were identified and included in our data analysis. The pooled risk ratio of CAD in patients with SSc was 1.82 (95 % CI, 1.40 to 2.36). The statistical heterogeneity of this meta-analysis was moderate with an I (2) of 73 %. Our study demonstrated a statistically significant increased CAD risk among patients with SSc.